There are 3.3 million perinatally HIV-infected (paHIV+) children living with HIV worldwide. PaHIV+ and HIV-exposed but uninfected (HEU) youth are both at risk for adverse cognitive and behavioral health outcomes. The vast majority of these youth live in low- and middle-income countries (LMIC) with over 200,000 paHIV+ and millions of HEU youth in Asia alone. With increased availability of effective antiretroviral treatment, the number of new cases, as well as child mortality has both decreased. But, providers are now challenged to meet the complex needs of a growing number of surviving youth who must cope with HIV as a chronic, highly stigmatized, and transmittable illness. With this rationale, we will identify critical determinants for resilience, defined as competence durin adolescence in cognitive, emotional and behavioral functioning in the face of adverse circumstances. Our central hypothesis is that paHIV+ youth will have compromised abilities relative to their HEU peers, but in both groups, critical determinants for competency will exist. We leverage the availability of paHIV+ and HEU children enrolled in the NIH-funded PREDICT study with up to 8 years of clinical, cognitive and neuroimaging follow-up. The PREDICT study showed less optimal neurodevelopment outcomes in paHIV+ ages 3-15 years compared to their HEU and HIV-unexposed/uninfected peers. As children progress through adolescence, it is critical to monitor the development of executive function, including decision making, planning, and self-regulation, and to understand the development of the frontal lobe and other brain areas that subserve executive function throughout life. This proposed work will examine higher cognition, executive, emotional and behavioral functioning, and identify the determinants of resilience in paHIV+ and HEU adolescents as guided by the modified social action theory (contextual, social regulation and motivation/capabilities factors). The study will also determine the neuroanatomical correlates for risk and resilience using novel techniques to measure brain volume and integrity with particular interest in the prefrontal cortex area. Moreover, in order to understand the needs of this population globally, the study will examine determinants of resilience across culturally settings by comparing the resulting data to similar data sets from two US and one South African cohorts. Our long-term goal is to translate knowledge on the determinants of resilience into preventive interventions that will promote health in millions of paHIV+ and HEU youth worldwide.